Psoriasis is a chronic, non-contagious skin disorder. It appears in many different forms and can affect any part of the body.
Currently, there is no cure for psoriasis. However, over the years a wide variety of topical and systemic treatment methods that inhibit the inflammation, cell proliferation, or cell differentiation have been developed. Treatment of psoriasis remains a challenge because of its chronic recurrent nature. Various topical and systemic therapies include anti-inflammatory agents, e.g., glucocorticoids; analgesics; chemically synthesized disease-modifying antirheumatic drugs (DMARDs), e.g., methotrexate and ciclosporin; antiproliferative agents, e.g., retinoids and vitamin D analogs; TNF-α blockers, e.g., etanercept, infliximab, adalimumab, and efalizumab; monoclonal antibodies against B cells, e.g., rituximab; T-cell activation blockers, e.g., abatacept; IL-1 blockers, e.g., anakinra; coal tar; and phototherapy.
These treatment methods have proven to be of limited value due to disadvantages such as cosmetic liabilities, severe side effects, high cost, and minimal or short-term efficacy.
Retinoids, as an alternative, are also known to influence keratinocyte differentiation and have proven to be effective in the treatment of a variety of keratinization disorders including psoriasis.
U.S. Pat. No. 6,353,029 discloses a topical solution composition comprising tretinoin, 4-hydroxy anisole, polyethylene glycol, an antioxidant, a chelating agent, a lower alkanol, and water.
U.S. Pat. No. 5,643,584 discloses a topical aqueous gel composition comprising unsolubilized micronized tretinoin particles, a surfactant selected from the group consisting of octoxynol and nonoxynol, a preservative, a gelling agent, and water.
PCT Publication No. WO 90/14833 discloses an aqueous gel vehicle for topical application to the skin comprising active ingredients such as retinoids, in particular tretinoin. The composition also includes an aqueous medium, a gelling agent, and an antioxidant.
U.S. Pat. Nos. 5,914,334 and 6,258,830 disclose topical gel compositions of tazarotene comprising poloxamer 407, polysorbate 40, and hexylene glycol for the treatment of acne and psoriasis.
A review of the prior art thus reveals topical pharmaceutical compositions of retinoids such as tretinoin and tazarotene for the treatment of skin disorders such as psoriasis. However, irritancy to the skin remains the common side effect, leading to a high level of patient non-compliance.
Acitretin, a metabolite of etretinate, is available as an oral capsule dosage form and is indicated for the treatment of severe psoriasis. As the use of acitretin is limited by its systemic side effects, and skin being the target organ for the treatment of psoriasis, there remains an unmet need for topical pharmaceutical compositions of acitretin with minimal or no systemic side effects and with reduced irritancy to the skin.
For a topical pharmaceutical composition, the solubilization and release of a drug from the composition remain the essential prerequisites to ensure effective treatment. As acitretin is poorly soluble in water, it remains a great challenge to develop a topical pharmaceutical composition in which acitretin is maximally solubilized and readily released from the composition into the skin.
The scientists of the present invention have now developed a topical pharmaceutical composition of acitretin with an acceptable level of efficacy for treating psoriasis and with reduced irritancy. Further, acitretin is found to be readily released from the composition into the skin. Also, said composition of the present invention is found to be stable.